The administration of intermittent cycles of interleukin-2 (IL-2) to patients with HIV infection was found to be associated with substantial and sustained increases in the number of peripheral blood CD4+ T lymphocytes. Despite these increases in the critical element of the immune system affected by HIV, IL-2 therapy was not associated with clinical benefit as defined by overall mortality and number of new AIDS-defining illnesses. CD4+ T cell increases induced by IL-2 were better maintained when IL-2 was used together with antiretroviral therapy. Interferon-alpha was found to have antiretroviral activity superior to that of AZT. This activity was transient and not associated with the development of strains of HIV resistant to Interferon-alpha.